Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• et al. [59] reported an electrochemical method for the synthesis of phosphorylation of oxindoles and indolo[2,1-a]isoquinoline-6(5H)-ones using Cp2Fe through a radical addition/cyclization reaction at room temperature under argon gas. This research shows that this method is effective with various

Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• through calcium catalysis [8][9][10]. Asymmetric synthesis has also been achieved via, e.g., 1,4-addition and [3 + 2] cycloaddition of 3-tetrasubstituted oxindoles with a calcium Pybox catalyst [11][12], or through enantioselective Friedel–Crafts and carbonyl–ene reactions [13]. Since the pioneering

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• electron-donating substituents at the para-position of the N-arylacrylamide led to good yields. In cases of meta-substitution, a mixture of C6 and C4-substituted oxindole products were obtained, whereas ortho-substitution resulted in the desired oxindoles in moderate yields. Nitrogen substitution was also

Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• ][30]. The reaction of curcumins with azodicarboxylates, Morita–Baylis–Hillman derived nitroallylic acetates and α-hydrazinonitroalkenes were also investigated [29][31][32]. Very recently, our group has exploited 3-olefinic oxindoles and nitrochromenes to unfold the reactivities of curcumins [33][34

• cascade triple-Michael (Michael/Michael/oxa-Michael) reaction between curcumins and isatylidene malononitriles, giving spiro-oxindoles in excellent yields and diastereoselectivities [36]. Sahu et al. introduced a one-pot multicomponent reaction of curcumin, arylaldehyde and 2-aminobenzothiazole to

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• dialdehyde molecules, synthesis of bioactive natural products like oxazolomycin, ottelione A, pestalalactone, nigricanin and other useful molecules of potential interest such as oxindoles, cyclooctadienones, mandelic acid derivatives have been represented. The high yielding methodologies, emphasizing

• Cannizzaro reaction. Microwave-assisted crossed-Cannizzaro reaction for the synthesis of 3,3-disubstituted oxindoles. Synthesis of porphyrin-based rings using the Cannizzaro reaction. Synthesis of phthalides and pestalalactone via Cannizarro–Tishchenko-type reaction. Synthesis of dibenzoheptalene bislactones

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• products (Scheme 59). The same year, Balaraman and co-workers reported the selective C-alkylation of oxindole with unactivated secondary alcohols catalyzed by a phosphine-free NNN-Mn(II) catalyst [89]. Various cyclic and aliphatic secondary alcohols were coupled with different oxindoles using 2 mol % of

• Mn23 and t-BuOK (30 mol %) in toluene at 110 °C for 8 h to afford the C3-alkylated oxindoles with up to 85% yield (Scheme 60). However, secondary alcohols substituted with reducible (nitro, amide, aldehyde) groups and −OH, −SH, and –NHMe groups did not provide any expected C-alkylated product. Like the

• ]. Various secondary alcohols were tested with oxindoles using 4 mol % of Mn25 as a pre-catalyst, t-BuOK (1.5–2 equiv.) as a base in toluene at 125 °C for 18 h to provide the C-3-alkylated oxindoles with good yields (70–87%). Moreover, substituting oxindole with different primary alcohols gave up to 85

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• -heterocycles. Recently, independent research groups led by Li, Yang, and Patureau separately disclosed a novel approach to 3,3-disubstituted oxindoles 43 through an iodide/phosphine-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides 42 (Scheme 18) [35][36

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• ) [70]. We expected that using olefinic oxindoles 14 as alkenes for the [3 + 2] cycloaddition could afford spirooxindole-pyrrolizidines. The method development revealed that recyclable zeolite HY acid is a good catalyst for the cycloaddition [70]. Thus, the zeolite HY-catalyzed reaction of glycine with

• two equiv each of arylaldehydes and olefinic oxindoles 14 in EtOH at 90 °C for 6 h gave bis[spirooxindole-pyrrolizidine] compounds 15a–g in 60–73% yields with up to 6:1 dr (Scheme 10). It is worth noting that this pseudo-five-component reaction gives butterfly-shaped molecules which have a plane of

• olefinic oxindoles to replace maleimides, the reactions gave spiro[indoline-tetrahydropyrrolothiazole] products 30 in 55–70% with greater than 4:1 dr [76]. The reaction mechanism suggests that the reaction of cysteine with arylaldehydes gives N,S-acetals 27 which convert to AMYs 28 after decarboxlyation

Synthesis of 5-arylidenerhodanines in L-proline-based deep eutectic solvent

• Stéphanie Hesse

Beilstein J. Org. Chem. 2023, 19, 1537–1544, doi:10.3762/bjoc.19.110

• compounds and allow, for example, the formation of rhodanine-fused spiro[pyrrolidine-2,3′-oxindoles] D having antidiabetic activity [6]. Thiazolidinediones and thiazolidinones were found to be potent moieties of a series of furan-2-ylmethylenethiazolidinediones E that were studied as selective ATP

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• sulfur reagents resulted in thiolated products 92 up to 99% ee, in the presence of quinidine as the organocatalyst (Scheme 38) [72]. For the study of enantioselectivity of products, different N-substituted oxindoles with H, Me, phenyl, and benzyl groups were investigated. As the size of N-protecting

• groups increased, the percentage of enantioselectivity decreased, where in the case of NH-oxindoles, the product was achieved with only 6% ee. Another sulfenylation at the 3-position of unprotected oxindoles with N-(phenylthio)phthalimide was reported by Feng et al. [73]. A chiral N,N′-dioxide-Sc(OTf)3

• complex as a catalyst and a Brønsted base were applied in the procedure. It is interesting to note that in such a method, sulfenylation of NH-oxindoles resulted in the thiolated products with excellent enantioselectivities (up to 99% ee). In 2013, sulfenylation and chlorination of β-ketoesters 93, and 95

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• (Scheme 28) [58]. In 2021, Wang, Jin and co-workers deployed chiral thiourea T2 as the catalytic agent for executing a highly enantioselective aza-Friedel–Crafts process between β-naphthols 119 and isatin-derived ketimines 49 in the course of accessing enantioenriched 3-amino-2-oxindoles 122 (Scheme 29

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• theory in N,N-dimethylformamide (SMD). Extended version of Figure 2 involving energies of final products can be found in Supporting Information File 1. Eschenmoser coupling reaction between 3-substituted oxindoles and thioamides. Possible reactions of α-haloketones, esters and amides with primary

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• afforded various functionalized oxindoles featuring a C3 quaternary stereogenic center. Mechanistic experiments suggest a radical mechanism. Keywords: decarboxylative cascade cyclization; iodide catalysis; metal-free photocatalysis; oxindole; phosphine catalysis; Introduction Radical-initiated cascade

• /cyclization cascades from acrylamides for the synthesis of oxindoles [39][40][41]. The radicals are typically generated from alkyl halides [42][43][44], carboxylic acids [45][46][47], simple alkanes [48], alkylboronic acids [49], isocyanides [50], or other [51][52][53]. In this context, the group of Fu

• disclosed a visible light-mediated radical tandem cyclization of N-arylacrylamides with N-(acyloxy)phthalimides to access 3,3-dialkylated oxindoles in the presence of [Ru(bpy)3Cl2]·6H2O [46]. However, these seminal methods remain limited by the need of noble-metal-based photocatalysts, excess additives and

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• oxindoles. High synthetic efficiency, operational simplification and reaction process economy using EtOH as solvent, and only releasing CO2 and H2O as side products confer this approach favorable in green chemistry metrics analysis. Keywords: azomethine ylides; cascade; double annulations; N,S-acetalation

A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles

• Pavel A. Topanov,
• Anna A. Maslivets,
• Maksim V. Dmitriev,
• Irina V. Mashevskaya,
• Yurii V. Shklyaev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2022, 18, 1532–1538, doi:10.3762/bjoc.18.162

• , Perm 614990, Russian Federation 10.3762/bjoc.18.162 Abstract There has been developed an easy synthetic approach to spiro[dihydrofuran-2,3'-oxindoles] via a highly diastereoselective formal [4 + 1] cycloaddition reaction of [e]-fused 1H-pyrrole-2,3-diones with diazooxindoles. The described novel

• natural products bearing a spirofuranoxindole moiety. Synthesis of spiro[dihydrofuran-2,3'-oxindoles] from enones and diazooxindoles. Cycloaddition reactions of [e]-fused 1H-pyrrole-2,3-diones. The model reaction of FPD 1a and diazooxindole 2a. The reaction of FPD 1k with diazooxindole 2a. A) Plausible

Tri(n-butyl)phosphine-promoted domino reaction for the efficient construction of spiro[cyclohexane-1,3'-indolines] and spiro[indoline-3,2'-furan-3',3''-indolines]

• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2022, 18, 669–679, doi:10.3762/bjoc.18.68

• functionalized spiro[cyclohexane-1,3'-indolines] in good yields and with good diastereoselectivity. On the other hand, the tri(n-butyl)phosphine-catalyzed reaction of 3-(ethoxycarbonylmethylene)oxindoles and bis-chalcones gave functionalized spiro[cyclohexane-1,3'-indolines] with different regioselectivity

• expand the scope of this reaction, 3-(ethoxycarbonylmethylene)oxindoles 4 were also employed in the reaction with bis-chalcones 2. We were pleased to find that the reaction proceeded smoothly in the presence of an excess amount of tri(n-butyl)phosphine under similar reaction conditions and the results

• isatylidene malononitriles or 3-(ethoxycarbonylmethylene)oxindoles for the efficient construction of two kinds of spiro[cyclohexane-1,3'-indolines] in good yields and with good diastereoselectivity. Additionally, tri(n-butyl)phosphine promoted the domino reaction of isatins and ethyl isatylidene cyanoacetates

Tosylhydrazine-promoted self-conjugate reduction–Michael/aldol reaction of 3-phenacylideneoxindoles towards dispirocyclopentanebisoxindole derivatives

• Sayan Pramanik and
• Chhanda Mukhopadhyay

Beilstein J. Org. Chem. 2022, 18, 469–478, doi:10.3762/bjoc.18.49

• derivatives were synthesized on the basis of Michael acceptor ability of 3-alkylidene oxindoles with various donor synthons [16][17][18][19][20][21][22]. However, in spite of the progress in the synthesis of dispirocyclopentanebisoxindoles with concise structural and stereochemical diversity, the one-pot

Unexpected chiral vicinal tetrasubstituted diamines via borylcopper-mediated homocoupling of isatin imines

• Marco Manenti,
• Leonardo Lo Presti,
• Giorgio Molteni and
• Alessandra Silvani

Beilstein J. Org. Chem. 2022, 18, 303–308, doi:10.3762/bjoc.18.34

• oxindoles [7][8][9][10][11] and also of aminoboronic acids [12], we recently exploited a molecular hybridization strategy to synthesize chiral oxindole-based β-aminoboronic acids and spiro derivatives [13]. Apart from our work and a quite recent report describing a useful Cu-catalyzed enantioselective

• intramolecular transformation [14], the insertion of a boron atom into chiral oxindoles is scarcely reported. Continuing with such previous project, next we looked at the copper-mediated reaction of isatin-derived, optically pure sulfinyl ketimines with bis(pinacolato)diboron, as a potential way to access

New advances in asymmetric organocatalysis

• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28

• catalysis relies on the deprotonation of one of the substrates, but basic conditions may limit the applicability of this methodology. A unique base-free variant of chiral phase-transfer catalytic alkylation of 2-oxindoles was developed by Connon and co-workers [23]. Pentacarboxycyclopentadienes are a unique

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• hydroxyamination of oxindoles and β-ketoamides [49][50][51][52][53][54]. Recently, it has been shown that malonate derivatives such as malonate half thioesters and malonamides could be effectively used in various enantioselecive addition reactions [55][56][57][58][59][60]. In this context, Chen and co-workers

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole

• Estelle Silm,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18

• malonates [25]. Herein, we report the results of an asymmetric organocatalytic Michael addition of CPD to alkylidene oxindoles. Results and Discussion Chiral multifunctional thioureas [26][27] and squaramides [28] are extensively used as catalysts in asymmetric Michael additions. We believed that a

• substituted oxindoles with an E-configuration of the double bond. The results are presented in Scheme 2. Both electron-withdrawing (Scheme 2, 3f–h) and electron-donating groups (Scheme 2, 3m,n) at the phenyl ring of the benzylidene moiety were tolerated. The position of the halide at the aromatic ring did not

• p-Me-substituted oxindole was also slow in reacting and the yield was moderate, but the enantioselectivity remained high (Scheme 2, 3n). The reaction tolerated alkylidene oxindoles, although the product was obtained in a slightly lower yield and enantioselectivity (Scheme 2, 3o). The reaction did

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• sections: strictly carbon CDC reactions and heteroatomic CDC reactions. Iron-catalyzed carbon–carbon cross dehydrogenative coupling In 2013, Li and co-workers reported the FeCl3-catalyzed arylalkylation of activated alkenes 60 for the synthesis of oxindoles 62 (Scheme 10) [80]. Mechanistic studies

• propagation sites it is terminated, typically through the generation of a new radical species. The Zhu group followed up on this work by disclosing the use of acetonitrile as the radical precursor for the cyanomethylation/arylation of arylacrylamides to access oxindoles [82]. Despite the small scope of

• reported a similar approach towards the assembly of 2,2-disubstituted indolines from N-sulfonylanilines and substituted styrene derivatives [93]. In 2014, the Jiao group investigated the carbosulfonation of alkenes 60 for the synthesis of oxindoles 90 through sequential C–S/C–C-bond formation (Scheme 16

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• reactions [34][35]. In 2015, Zhao et al. synthesized spiro[pyrrolidine-3,3'-oxindoles] 29 in single step by asymmetric cascade aza-Michael/Michael addition reaction between 4-tosylaminobut-2-enoates 27 and 3-ylideneoxindoles 26 catalyzed by a chiral bifunctional tertiary amine, squaramide (cat. 28) which

• -nitrophthalimide to α,β-unsaturated ketones. Diastereoselective synthesis of bridged 1,2,3,4-tetrahydroisoquinoline derivatives using modularly designed organocatalyst. Synthesis of spiro[pyrrolidine-3,3'-oxindoles] via asymmetric cascade aza-Michael reaction catalyzed by squaramide. Asymmetric aza-Michael